RESUMEN
BACKGROUND: Apolipoprotein E (ApoE) plays a major role in lipid homeostasis and myelination in the central nervous system. Although ApoE gene variants have been linked with cognitive impairment in the setting of Multiple sclerosis (MS), no association with disease susceptibility was found, while similar studies in pediatric-onset MS (POMS) are limited. OBJECTIVE: This study aims to explore the role of ApoE gene variants in the POMS susceptibility of a Hellenic cohort and any association with disease features. METHODS: 112 POMS, fulfilling the revised IPMSSG 2013 criteria, 391 adult-onset MS (AOMS) and 200 healthy controls (HCs), were enrolled. After DNA extraction, ApoE genotyping was performed by a polymerase chain reaction and sequence-specific-oligonucleotide technique. RESULTS: ApoE2/E3 genotype and ApoE2 allele were found to be significantly more frequent among POMS patients compared to HCs [(20.5% vs 11 %, OR [95 %]: 2.1 (1.1-4.0), p = 0.03)], and [(11% vs 5.3 %, OR [95 %]: 2.3 (1.2-4.1), p = 0.01)], respectively. Additionally, significantly lower frequencies of the ApoE3/E3 genotype and the ApoE3 allele were observed in POMS patients compared to HCs (59.8% vs 79 %, OR [95 %]:0.40 (0.24-0.65), p = 0.0005 and 79% vs 89 % 0.46, OR [95 %]: (0.30-0.73), p = 0.001)], respectively. CONCLUSIONS: The ApoE2 allele may represent a novel risk factor for POMS development.
RESUMEN
Antigen presentation is a crucial mechanism that drives the T cell-mediated immune response and the development of Multiple Sclerosis (MS). Genetic alterations within the highly variable Major Histocompatibility Complex Class II (MHC II) have been proven to result in significant changes in the molecular basis of antigen presentation and the clinical course of patients with both Adult-Onset MS (AOMS) and Pediatric-Onset MS (POMS). Among the numerous polymorphisms of the Human Leucocyte Antigens (HLA), within MHC II complex, HLA-DRB1*15:01 has been labeled, in Caucasian ethnic groups, as a high-risk allele for MS due to the ability of its structure to increase affinity to Myelin Basic Protein (MBP) epitopes. This characteristic, among others, in the context of the trimolecular complex or immunological synapsis, provides the foundation for autoimmunity triggered by environmental or endogenous factors. As with all professional antigen presenting cells, macrophages are characterized by the expression of MHC II and are often implicated in the formation of MS lesions. Increased presence of M1 macrophages in MS patients has been associated both with progression and onset of the disease, each involving separate but similar mechanisms. In this critical narrative review, we focus on macrophages, discussing how HLA genetic alterations can promote dysregulation of this population's homeostasis in the periphery and the Central Nervous System (CNS). We also explore the potential interconnection in observed pathological macrophage mechanisms and the function of the diverse structure of HLA alleles in neurodegenerative CNS, seen in MS, by comparing available clinical with molecular data through the prism of HLA-immunogenetics. Finally, we discuss available and experimental pharmacological approaches for MS targeting the trimolecular complex that are based on cell phenotype modulation and HLA genotype involvement and try to reveal fertile ground for the potential development of novel drugs.
Asunto(s)
Alelos , Macrófagos , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/genética , Esclerosis Múltiple/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase II/inmunología , Presentación de Antígeno/genética , Predisposición Genética a la Enfermedad , Animales , Polimorfismo GenéticoRESUMEN
BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system, often leading to poor sleep quality and diminished quality of life (QoL) for affected patients. Sleep disturbances in MS do not always correlate linearly with other symptoms such as anxiety, depression, fatigue, or pain. Various approaches, including stress reduction techniques such as mindfulness-based interventions, have been proposed to manage MS-related sleep issues. OBJECTIVE: The aim of this study was to evaluate the effects of the mindfulness-based body scan technique on sleep quality and QoL in patients with MS using both subjective (questionnaires) and objective (electronic portable device) measures. METHODS: A single-case study was performed involving a 31-year-old woman diagnosed with relapsing-remitting MS. The patient practiced the mindfulness-based body scan technique daily before bedtime and outcomes were compared to measures evaluated at baseline. RESULTS: The mindfulness-based body scan intervention demonstrated positive effects on both sleep quality and overall QoL. Biometric data revealed a notable dissociation between daily stress levels and sleep quality during the intervention period. Although self-report instruments indicated significant improvement, potential biases were noted. CONCLUSIONS: While this study is limited to a single patient, the promising outcomes suggest the need for further investigation on a larger scale. These findings underscore the potential benefits of the mindfulness-based body scan technique in managing sleep disturbances and enhancing QoL among patients with MS.
RESUMEN
Autoimmune diseases of the central nervous system (CNS) such as multiple sclerosis (MS) are only partially represented in current experimental models and the development of humanized immune mice is crucial for better understanding of immunopathogenesis and testing of therapeutics. We describe a humanized mouse model with several key features of MS. Severely immunodeficient B2m-NOG mice were transplanted with peripheral blood mononuclear cells (PBMCs) from HLA-DRB1-typed MS and healthy (HI) donors and showed rapid engraftment by human T and B lymphocytes. Mice receiving cells from MS patients with recent/ongoing Epstein-Barr virus reactivation showed high B cell engraftment capacity. Both HLA-DRB1*15 (DR15) MS and DR15 HI mice, not HLA-DRB1*13 MS mice, developed human T cell infiltration of CNS borders and parenchyma. DR15 MS mice uniquely developed inflammatory lesions in brain and spinal cord gray matter, with spontaneous, hCD8 T cell lesions, and mixed hCD8/hCD4 T cell lesions in EAE immunized mice, with variation in localization and severity between different patient donors. Main limitations of this model for further development are poor monocyte engraftment and lack of demyelination, lymph node organization, and IgG responses. These results show that PBMC humanized mice represent promising research tools for investigating MS immunopathology in a patient-specific approach.
Asunto(s)
Encéfalo , Linfocitos T CD8-positivos , Modelos Animales de Enfermedad , Cadenas HLA-DRB1 , Esclerosis Múltiple , Médula Espinal , Animales , Humanos , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/genética , Ratones , Cadenas HLA-DRB1/genética , Linfocitos T CD8-positivos/inmunología , Médula Espinal/inmunología , Médula Espinal/patología , Encéfalo/patología , Encéfalo/inmunología , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/genética , Encefalomielitis Autoinmune Experimental/patología , Linfocitos T CD4-Positivos/inmunología , FemeninoRESUMEN
BACKGROUND: Pediatric-Onset Multiple Sclerosis (POMS) is considered a complex disease entity and several genetic, hormonal, and environmental factors have been associated with disease pathogenesis. Linkage studies in Caucasians have consistently suggested the human leukocyte antigen (HLA) polymorphisms, as the genetic locus most strongly linked to MS, with the HLA-DRB1*15:01 allele, being associated with both adult and pediatric MS patients. Here we aim to investigate the prevalence of the HLA-DRB1 alleles among a Hellenic POMS cohort and any possible associations with clinical and imaging disease features. MATERIALS AND METHODS: 100 POMS patients fulfilling the IPMSSG criteria, 168 Adult-Onset MS (AOMS) patients, and 246 Healthy Controls (HCs) have been enrolled. HLA genotyping was performed with a standard low-resolution sequence-specific oligonucleotide (SSO) technique. RESULTS: POMS patients display a significantly increased HLA-DRB1*03 frequency compared to both HCs [24% vs. 12.6%, OR [95%CI]: 2.19 (1.21-3.97), p=0.016) and AOMS (24% vs. 13.1%, OR [95%CI]: 2.1 (1.1-3.98), p=0.034] respectively. HLA-DRB1*03-carriers display reduced risk for brainstem lesion development (OR [CI 95%]:0.19 (0.06-0.65), p=0.011). A significantly lower frequency of HLA-DRB1*07 (4% vs 13.4%, OR (95% CI): 0.27 (0.09-0.78), p= 0.017) and HLA-DRB1*11 (37% vs 52%, OR [95% CI]: 0.54 (0.34-0.87), p= 0.016) was observed in POMS compared to HCs. CONCLUSION: The HLA-DRB1*03 allele was associated with a higher risk for POMS, replicating our previous findings, and with a lower risk for brainstem lesion development, a common clinical and neuroimaging feature in POMS, while HLA-DRB1*07 and HLA-DRB1*11 display a protective role. These findings expand the existing knowledge of HLA associations and POMS.
RESUMEN
Antibodies to glutamic acid decarboxylase (GAD) have been predominantly associated with stiff-person syndrome (SPS), which is often accompanied by organ-specific autoimmune diseases, such as late-onset type 1 diabetes. Autoimmune retinal pathology in SPS has recently been suggested to coexist in patients suffering from this disease; however, evidence reporting potential treatment options for the neurological and visual symptoms these patients experience remains scarce. We provide a review of the relevant literature, presenting a rare case of a middle-aged woman with autoimmune retinopathy (AIR) followed by stiff-leg syndrome who responded to intravenous immune globulin treatment (IVIg). Our report adds to previously reported data supporting the efficacy of IVIg in SPS spectrum disorders while also proposing the potential effect of IVIg in treating SPS spectrum patients with coexisting AIR.
RESUMEN
The aim was to evaluate the performance of the latest quantitative marker for intrathecal IgG synthesis and to compare it with other established markers used for the same purpose. We retrospectively applied Auer's and Reiber's intrathecal IgG synthesis formulae in a cohort of 372 patients under investigation for central nervous system demyelination who had undergone lumbar puncture and oligoclonal bands (OCBs) detection for demonstrating intrathecal IgG synthesis. A ROC analysis revealed Auer's formula had lower sensitivity (68%) compared to Reiber's formula (83%) and IgG index (89%), in our cohort of patients that exhibited normal to mildly elevated albumin quotients (4.48 ± 3.93). By excluding possible sources of errors, we assume that Auer's formula is less sensitive than other established tools for the "prediction" of the detection of OCBs in routine cerebrospinal fluid (CSF) analyses due to the mathematical model used. Given the ability of Reiber's hyperbolic formula to describe the blood-CSF IgG distribution across a wide range of blood-brain barrier functionality, its use and the use of similar formulae are recommended for the discrimination between CNS-derived and blood-derived molecules in clinical laboratories.
RESUMEN
High-dose intravenous steroid treatment (HDIST) represents the first choice of treatment for multiple sclerosis (MS) relapses. Chronic oral glucocorticoid (GC) administration correlates with bone loss whereas data regarding HDIST in MS are still conflicting. Twenty-five newly diagnosed MS patients (NDMSP) (median age: 37 years) were prospectively studied for the effects of HDIST on bone mineral density (BMD) and bone metabolism. Patients received 1000 mg methylprednisolone intravenously every day for 5 days followed by oral prednisolone tapering over 21 days. Bone metabolism indices were determined prior to GC, on days 2, 4, 6, and 90, and at months 6, 12, 18, and 24 post GC therapy. Femoral, lumbar-spine BMD, and whole-body measurement of adipose/lean tissue were assessed prior to GC-administration and then every six months. Ten patients completed the study. N-terminal-propeptide-procollagen-type-1 and bone-specific alkaline phosphatase showed a significant increase at day-90 (p < 0.05). A transient non-significant fall of BMD was observed at 6 months after GC-administration, which subsequently appeared to be restored. We conclude that HDIST seems not to have long-term negative effects on BMD, while the observed transient increase of bone formation markers probably indicates a high bone turnover phase to GC-administration. Additional prospective studies with larger sample size are needed.
RESUMEN
Autoimmune thyroid disease (AITD) is the most common adverse effect in alemtuzumab (ALZ) treated relapsing-remitting (RR) multiple sclerosis (MS) patients. The objective of this prospective study was to analyze the occurrence, timing of onset, clinical course, and laboratory characteristics of AITD post-ALZ. We evaluated 35 RRMS patients treated with ALZ at a single academic MS center; clinical and laboratory data were collected before ALZ initiation and thereafter quarterly on follow-up with a median of 43.5 months. Seventeen out of 31 patients (54.8%) with no prior history of thyroid dysfunction developed AITD with a mean onset of 19.4 months ± 10.2 (SD) after the first ALZ cycle; Graves' disease (GD) (n = 9); hypothyroidism with positive stimulating thyrotropin receptor antibodies (TRAb) (n = 1); Hashimoto thyroiditis (HT) (n = 6); HT with hypothyroidism (n = 1). Interestingly, seven of nine (77.7%) GD patients showed a fluctuating course. Three out of four patients with preexisting thyroid disease remained stable, whereas one with prior HT and hypothyroidism developed fluctuating GD. All patients with GD commenced antithyroid drugs (ATDs); five continued on "block and replace" treatment; one required radioactive iodine, and one total thyroidectomy. Our analysis showed earlier onset of ALZ-induced AITD in comparison to most other ALZ cohorts; overall, these patients required complex therapeutic approaches of the AITD. We observed a higher rate of fluctuating GD, with earlier onset and lower remission rate than previously reported, which in the majority of patients required prolonged "block and replace" therapy in the minimum dose of each therapeutic agent or more definitive interventions.
Asunto(s)
Enfermedad de Graves , Hipotiroidismo , Esclerosis Múltiple , Enfermedades de la Tiroides , Neoplasias de la Tiroides , Humanos , Alemtuzumab/efectos adversos , Esclerosis Múltiple/inducido químicamente , Esclerosis Múltiple/tratamiento farmacológico , Estudios Prospectivos , Autoinmunidad , Radioisótopos de Yodo/efectos adversos , Enfermedades de la Tiroides/inducido químicamente , Enfermedades de la Tiroides/epidemiología , Hipotiroidismo/inducido químicamenteRESUMEN
OBJECTIVES: Long-term immunomodulatory therapy of pediatric onset-multiple sclerosis (POMS) is based mainly on published case series and internationally agreed guidelines. Relevant studies in the Greek population are absent from the literature. The purpose of this study is to present data on the efficacy and safety of the 1st line immunomodulatory drugs in the treatment of POMS patients. MATERIALS AND METHODS: The present study included 27 patients meeting the IPMSSG criteria for POMS and who are monitored at the outpatient clinic of the Multiple Sclerosis and Demyelinating Diseases Unit (MSDDU), of the 1st Neurological Department, University Hospital of Aeginition. All patients received 1st line immunomodulatory drugs as initial therapy. Clinical, laboratory, and imaging parameters of the disease were recorded before and after treatment. RESULTS: Post-treatment, a significant reduction of the relapse number (mean ± SD: 2.0 ± 1.0 vs 1.2 ± 1.6, p = 0.002), EDSS progression (mean ± SD: 1.5 ± 0.8 vs 0.9 ± 0.7, p = 0.005) and ARR (mean ± SD: 1.5 ± 0.7 vs 0.4 ± 0.5, p = 0.0001) was observed, while no changes were observed in the EDSS score, (mean ± SD: 1.8 ± 0.6 vs 1.9. 0.6, p = 0.60). Advanced age at treatment initiation increased the risk for drug discontinuation before 24 months of therapy (HR = 0.6, 95% CI (0.35-0.99), p = 0.04). CONCLUSIONS: Most pediatric patients are forced to switch to either more efficacious 1st line or 2nd line drugs. Additionally, our study suggests that older age at the time of the 1st line treatment initiation, contributes to earlier drug discontinuation.
Asunto(s)
Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Niño , Preescolar , Esclerosis Múltiple/tratamiento farmacológico , Grecia/epidemiología , Agentes Inmunomoduladores , Estudios Retrospectivos , Insuficiencia del Tratamiento , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológicoRESUMEN
Multiple sclerosis (MS) and its various comorbidities that may be observed are of great interest due to the complexity of MS pathophysiology and all of the immunological changes that follow. The incidence of cancer in MS has been investigated for several years, as not only does it affect ongoing therapeutical decisions, but also, certain disease-modifying treatments (DMTs) may increase the risk of tumorigenesis. For the first time, we present a case of a female patient with pediatric-onset MS (POMS) and multiple endocrine neoplasia 2B (MEN2B) and analyze the immunological impact of these diseases on the therapeutical choice, under the umbrella of her COVID-19 infection and the SARS-CoV-2 pandemic as a whole. We also review the existing literature regarding the immunogenetic and immunological correlations between these two extremely rare diseases and discuss the most suitable treatment for our case, which seems to be an anti-CD20 agent due to a better outcome in putative MS worsening and tumor progression, when killer immunoglobulin-like receptors' (KIR) expression is reduced in natural killer (NK) cells. We also broaden our concerns on this comorbidity issue, at the same time focusing on the future research needed in this unexplored field of the comorbidity of MS and cancers.
Asunto(s)
Enfermedad Mixta del Tejido Conjuntivo , Síndrome de Leucoencefalopatía Posterior , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Síndrome de Sjögren/tratamiento farmacológico , Síndrome de Leucoencefalopatía Posterior/diagnóstico por imagen , Síndrome de Leucoencefalopatía Posterior/etiología , Anticuerpos AntinuclearesRESUMEN
This article recapitulates the evidence on the role of mammalian targets of rapamycin (mTOR) complex pathways in multiple sclerosis (MS). Key biological processes that intersect with mTOR signaling cascades include autophagy, inflammasome activation, innate (e.g., microglial) and adaptive (B and T cell) immune responses, and axonal and neuronal toxicity/degeneration. There is robust evidence that mTOR inhibitors, such as rapamycin, ameliorate the clinical course of the animal model of MS, experimental autoimmune encephalomyelitis (EAE). New, evolving data unravel mechanisms underlying the therapeutic effect on EAE, which include balance among T-effector and T-regulatory cells, and mTOR effects on myeloid cell function, polarization, and antigen presentation, with relevance to MS pathogenesis. Radiologic and preliminary clinical data from a phase 2 randomized, controlled trial of temsirolimus (a rapamycin analogue) in MS show moderate efficacy, with significant adverse effects. Large clinical trials of indirect mTOR inhibitors (metformin) in MS are lacking; however, a smaller prospective, non-randomized study shows some potentially promising radiological results in combination with ex vivo beneficial effects on immune cells that might warrant further investigation. Importantly, the study of mTOR pathway contributions to autoimmune inflammatory demyelination and multiple sclerosis illustrates the difficulties in the clinical application of animal model results. Nevertheless, it is not inconceivable that targeting metabolism in the future with cell-selective mTOR inhibitors (compared to the broad inhibitors tried to date) could be developed to improve efficacy and reduce side effects.
Asunto(s)
Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Serina-Treonina Quinasas TOR , Animales , Ensayos Clínicos Fase II como Asunto , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Humanos , Ratones , Ratones Endogámicos C57BL , Esclerosis Múltiple/patología , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Transducción de Señal , Sirolimus/farmacología , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
The exact immunopathogenesis, genetic mechanisms and triggering factors underlying myasthenia gravis (MG) and neuromyelitis optica (NMO) remain unknown and the coexistence may underline an aetiopathogenetic link be- tween these two diseases. We report the cases of two thymectomized patients with acetylcholine receptor (AChR) antibody (Ab)-positive MG who eventually developed AQP4-NMO. Next-Generation Sequencing (NGS) analysis showed that patient-1 had two HLA alleles previously associated with MG, mainly HLA-A*01:01:01 and HLA-DRB1*03:01, present in a haplotype in Caucasian MG patients (HLA-A1-B8-DR3-DQ2). Patient-2, expressed HLA-C*07:01:01, a well characterized MG risk factor and HLA-DQB1*05:02:01, previously described both in MG and NMO patients. Finally, we observed two common alleles in patient 1 and 2, HLA-DQA1*05:01:01 and HLA-DPB1*04:02:01. We believe that this study provides clinical evidence of the role of specific HLA alleles in rare forms of combined human peripheral and CNS autoimmunity, a fact that enhances the aim towards tailor-made therapeutic decision making.
Asunto(s)
Miastenia Gravis , Neuromielitis Óptica , Alelos , Autoanticuerpos , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Miastenia Gravis/complicaciones , Miastenia Gravis/genética , Neuromielitis Óptica/complicaciones , Neuromielitis Óptica/genética , Receptores ColinérgicosRESUMEN
BACKGROUND: Hereditary angioedema (HAE) related to C1 esterase-inhibitor deficiency activates the classic complement pathway and results to edematous crises. Although HAE is usually associated with multiple immunoregulatory disorders, neurologic manifestations are rare. CASE REPORT: We report on the case study of a 33-year-old man diagnosed with HAE (SERPIN1G gene mutation) and multiple sclerosis (MS), followed up for at least 6 years. After a first clinical attack of HEA with scrotal edema, MS disease exacerbation was observed. Treatment with glatiramer acetate could not prevent either MS or HAE clinical attacks with recurrent exacerbations been observed. Remission of MS and significant amelioration of HAE attacks were achieved under fingolimod treatment. CONCLUSIONS: Herein we provide long term evaluation of an extremely rare case of concomitant existence of HAE and MS and present the effects of MS current disease-modifying therapies in HAE attacks. Our case highlights the possible effect of fingolimod in immunoregulatory-mechanisms implicated in both diseases.
RESUMEN
Pediatric-onset multiple sclerosis (MS, POMS) accounts for 3-5% of all MS cases and is characterized by a highly inflammatory profile, often warranting treatment with high-efficacy agents. Our aim is to present real-world data of a series of 18 Hellenic POMS patients treated with natalizumab (NTZ) either as adolescents or as adults, after high disease activity has efficiently subsided. Clinical and imaging/laboratory data from 18 POMS patients who have received at least one NTZ infusion were selected in this single-center retrospective observational study. Human leukocyte antigen (HLA) genotyping was performed with standard low-resolution sequence-specific oligonucleotide techniques. Eighteen patients with a mean age of disease onset of 15.3 ± 2.4 years were treated with NTZ with a mean of 51.7 ± 46.4 infusions, 6 as adolescents and 12 as adults. 22.2% were treatment naïve. At the end of the observational period, patients of both groups remained relapse-free, with no radiological activity and significantly reduced disability accumulation. No evidence of disease activity (NEDA)-3 status was achieved in 66.7% of all patients, 58.3% in the adult-treated, and 83.3% in the adolescent-treated POMS patients. NTZ was generally well tolerated. Only 5 adverse events were observed, in 3 patients who were carriers of the HLA-DRB1*15 (HLA-DRB1*15/HLA-DRB1*11 and HLA-DRB1*15/HLA-DRB1*13 genotypes), 1 homozygous for the HLA-DRB1*03 allele and 1 heterozygous for HLA-DRB1*04 and HLA-DRB1*16 alleles. NTZ is highly efficacious and mostly safe for POMS patients with high disease activity in all age groups. The role of immunogenetics in personalized patient evaluation and treatment needs to be further investigated.
Asunto(s)
Esclerosis Múltiple , Natalizumab , Adolescente , Niño , Grecia , Cadenas HLA-DRB1/genética , Humanos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/genética , Natalizumab/uso terapéutico , Estudios RetrospectivosRESUMEN
BACKGROUND: Cortical demyelination and meningeal inflammation have been detected neuropathologically in multiple sclerosis (MS) and recently in myelin oligodendrocyte glycoprotein antibody disease (MOGAD). OBJECTIVES: To assess in vivo cortical and leptomeningeal involvement in MOGAD. METHODS: We prospectively evaluated 11 MOGAD and 12 relapsing-remitting MS (RRMS) patients combining three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) and 3D-T1-weighted (3D-T1w) sequences at 3-Tesla magnetic resonance imaging (MRI). Leptomeningeal contrast enhancement (LMCE) was assessed on 3D-FLAIR post-gadolinium (3D-FLAIRGd). Cerebral cortical lesions (CCLs) were classified as either intracortical-subpial (IC-SP) or leukocortical (LC). RESULTS: CCLs were present in 8/11 MOGAD and 12/12 RRMS patients, with the number of CCLs being significantly lower in MOGAD (median (interquartile range (IQR)) 3 (0.5-4) vs 12 (4.75-19), p = 0.0032). In MOGAD, IC-SP lesions were slightly more prevalent than LC lesions (2 (0-2.5) vs 1 (0-2), p = 0.6579); whereas in RRMS, IC-SP lesions were less prevalent than LC lesions (3.5 (2.75-5.5) vs 9 (2-12.75), p = 0.27). LMCE was observed in 3/11 MOGAD and 1/12 RRMS patients; MOGAD with LMCE showed an increased median number of CCLs compared with MOGAD without LMCE (8 (4-9) vs 2.5 (0.75-3.25), p = 0.34). No correlation was observed between MOGAD MRI findings and (a) MOGAD duration, (b) serum MOG-immunoglobulin G1 titers, and (c) oligoclonal band presence. CONCLUSION: We described cortical lesion topography and detected for the first time LMCE using 3D-FLAIRGd sequences in MOGAD patients.
Asunto(s)
Imagen por Resonancia Magnética , Esclerosis Múltiple , Humanos , Imagenología Tridimensional , Inflamación/patología , Imagen por Resonancia Magnética/métodos , Meninges/diagnóstico por imagen , Meninges/patología , Esclerosis Múltiple/patología , Glicoproteína Mielina-OligodendrócitoRESUMEN
Stress has deleterious effects on brain health and yet, the prognostic value of psychosocial stress regarding the most common types of dementias, including Alzheimer disease, is still unclear. The primary aim of this systematic review was to explore the association between psychosocial stress and late onset dementia. We classified 24articles from Medline, PsycINFO, CINAHL, and Web of Science, as pertaining toxic categories of psychosocial and trauma-related stress (low socio-economic status [SES] related inequalities, marital status, posttraumatic stress disorder, work stress, "vital exhaustion" [VE], and, combined stressors). Using the Quality of Prognosis Studies in Systematic Reviews tool, we judged the quality of evidence to be low. This systematic review provided some non-robust, yet suggestive evidence that the above psychosocial types of stress are associated with increased risk of dementia in later life. Future robust, longitudinal studies with repeated validated measures of psychosocial stress and dementiaare required to strengthen or refute these findings.
Asunto(s)
Enfermedad de Alzheimer , Trastornos por Estrés Postraumático , Humanos , Enfermedad de Alzheimer/epidemiología , Estudios Longitudinales , Trastornos por Estrés Postraumático/epidemiologíaRESUMEN
BACKGROUND: Pediatric onset multiple sclerosis(POMS) is characterized by a highly active profile, often warranting treatment with high efficacy disease-modulating therapies (DMTs). Fingolimod, an oral sphingosine-1-phosphate receptor modulator, is the first Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved DMT for the treatment of POMS. OBJECT: Our aim is to present real-world data of seven fingolimod-treated POMS-patients, recruited in a single MS center in Greece. METHODS: Clinical and imaging/laboratory data from 7 Hellenic patients fulfilling the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for POMS diagnosis, who have received fingolimod treatment, were selected. Human leukocyte antigen (HLA) genotyping was performed with standard low-resolution sequence-specific oligonucleotide techniques. RESULTS: Three patients were treatment-naïve adolescents who received fingolimod as first-line treatment. Two experienced ongoing clinical and radiological disease activity and have been switched to natalizumab. The remaining cases were post-adolescent adults with POMS, where the vast majority experienced total/near-total disease remission. Fingolimod was generally well-tolerated. Two patients with high disease activity carried the HLA-DRB1*03 allele, while five patients were carriers of at least one of the HLA-DRB1*04, HLA-DRB1*13, and HLA-DRB1*14 alleles, which when not combined with HLA-DRB1*03 showed a trend towards a more favorable clinical course. Fingolimod responders showed a trend towards increased CD(16-56)+NK cell counts in immunophenotyping assays. CONCLUSIONS: Our preliminary results support that response of POMS patients to fingolimod may be partially dependent on age and previous DMT, with younger and treatment-naïve patients presenting worse outcomes. The role of immunogenetics and immunophenotyping in personalized treatment warrants investigation in larger and more diverse populations.